Evaluation of expected clinical success of tigecycline and other commonly used antimicrobials for empiric treatment of complicated skin and skin structure infections in Germany, Spain and the United States

Abstract number: 1733_1541

Mallick R., Fritsche T., Jones R., Kuznik A., Stilwell M., Sader H.

Objective: To model the expected clinical success of tigecycline and commonly used antimicrobials for empiric treatment of complicated skin and skin structure infections (cSSSI) based on evaluation of antimicrobial susceptibility and frequency of pathogen occurrence from a global surveillance programme. Tigecycline is a novel semisynthetic glycylcycline recently approved for parenteral treatment of cSSSI and intraabdominal infections in the United States (US) and European countries.

Methods: Consecutive, nonduplicate bacterial isolates collected between 2000 and 2005 from patients with documented cSSSI in 48 medical centres located in Germany (7), Spain (3), and the US (38) were used to evaluate the frequency of pathogen occurrence and susceptibility rates of tigecycline and select parenteral antimicrobials. All isolates were tested using CLSI broth microdilution methods and interpretive criteria. Tigecycline breakpoints approved by the USA-FDA were used. By applying pathogen-specific susceptibility rates to the frequency of occurrence of pathogens in each country, we calculated the overall expected coverage for each antimicrobial agent or combination.

Results: The top 3 pathogens identified in Germany and Spain were (frequency [%] by country): S. aureus (35.1 and 33.3%, respectively), E. coli (11.3 and 12.8%), and P. aeruginosa (11.0 and 12.6%). In the US, the top 3 pathogens identified were S. aureus (48.1%), P. aeruginosa (9.4%) and enterococci (8.8%). Other frequently isolated pathogens included b-haemolytic streptococci, Enterobacter and Klebsiella spp., with some inter-country variation. The rates of oxacillin-resistance (MRSA) varied from 3.6% in Germany to 17.3% in Spain and 43.5% in the US. Tigecycline was highly active (>90% S) against the most common pathogens, except P. aeruginosa and P. mirabilis. The overall expected coverage of cSSSI for the antimicrobials evaluated is summarised in the table.

Antimicrobial

Overall expected coverage (% susceptible of all pathogens)

Germany

Spain

USA

Tigecycline

87.5

85.1

90.6

Vancomycin

66.9

59.5

73.4

Linezolid

66.9

59.5

74.4

Levofloxacin

88.3

84.6

75.7

Piperacillin/tazobactam

96.0

90.0

75.6

Imipenem

95.8

92.1

74.1

Cefazolin

73.2

66.2

60.1

Ceftriaxone

80.2

74.3

64.0

Vancomycin & Piperacillin/tazobactam

98.2

95.8

95.7

Vancomycin & Levofloxacin

95.5

93.1

93.8

Conclusion: Vancomycin in combination with piperacillin/tazobactam had the highest overall expected empiric coverage of cSSSI in the countries evaluated. Among monotherapies, tigecycline had the highest expected coverage rate in the US, where the prevalence of MRSA was relatively high. Piperacillin/tazobactam and imipenem had the highest expected coverage in Germany and Spain, where the prevalence of MRSA was relatively low. Our results suggest that tigecycline might be a viable option for empiric treatment of cSSSI in these countries, especially in settings with high MRSA rates.